Understanding Biosimilars

The development and production of any protein biologic relies on
sound and robust structural data to demonstrate that the correct
molecule has been produced. The data should allow an assessment of all
relevant attributes of the molecule, and, from these data, in
conjunction with bioassay information, conclusions can be drawn
regarding structure and function. This is particularly true for
biosimilars where analytical data is the foundation of any biosimilarity
claim.

In a structural sense, the most common question that needs to be
answered is “Is the amino acid sequence of my molecule correct?” This is
true of novel biologics, where recombinant forms of a natural product
are being produced, and is also critical for biosimilar production,
where it is essential that the amino acid sequence of the biosimilar is
shown to be the same as that of the innovator. Whatever the product, if
the sequence is not as expected or comparable with an innovator, then
the production process must be corrected before further development can
be considered.

With the rise of modern analytical technologies such as mass
spectrometry and its ability to generate significant structural
information from proteins, sequence determination at the protein level
has become more feasible. Sequence analysis at this stage (rather than
DNA level) is able to confirm that correct translation has taken place
and demonstrate that no issue has arisen with codon usage. Indeed,
regulatory authorities are now expecting that amino acid sequence
information is generated to provide confirmation of the comparability of
biosimilar/innovator protein sequences, rather than relying on the DNA
sequences alone. For example, the EMA Biosimilar Guideline states, “The
target amino acid sequence of the biosimilar should be confirmed and is
expected to be the same as for the reference medicinal product.” The
comparable US FDA biosimilar guideline states, “It is expected that the
expression construct for a proposed product will encode the same primary
amino acid sequence as its reference product.” (1-2).

Dr Richard Easton obtained his PhD in glycoprotein structural characterisation using MS from Imperial College of Science, Technology and Medicine, UK. He subsequently spent several years there as a postdoctoral research scientist working in the field of glycoprotein structural characterisation with emphasis on glycan elucidation. He moved to GlaxoSmithKline for a short time where he was head of MS for the toxicoproteomics and safety assessment group. Richard joined M-Scan (now part of SGS Life Sciences) as a biochemist and became the Team Leader for Carbohydrate Analysis before being appointed Principal Scientist. He joined BioPharmaSpec in 2016 as Technical Director for Structural Analysis and is responsible for management of all aspects of carbohydrate and glycoprotein characterisation at the primary structure level.

Dr Andrew Reason is the founder, CEO, and Managing Director at BioPharmaSpec. He has 25 years of experience in analysis of both novel and biosimilar biopharmaceuticals and has been involved in the commercialisation of a number of analytical methods for characterising proteins. In addition to his scientific and managerial duties, Andrew has contributed to many industry publications and is a regular presenter at conferences. Andrew is also currently a Visiting Professor at the University of Warwick.

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